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基于GRB2/ERK/CRLS1通路探讨益肺宣肺降浊方对血管性痴呆模型大鼠的改善作用机制
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| 篇名： | 基于GRB2/ERK/CRLS1通路探讨益肺宣肺降浊方对血管性痴呆模型大鼠的改善作用机制 |
| TITLE： | Study on the improving mechanism of Yifei xuanfei jiangzhuo formula on vascular dementia model rats based on the GRB2/ERK/CRLS1 pathway |
| 摘要： | 目的 基于生长因子受体结合蛋白2（GRB2）/胞外信号调节激酶（ERK）/心磷脂合成酶1（CRLS1）通路，探讨益肺宣肺降浊方（YFXF）对血管性痴呆（VAD）模型大鼠的改善作用机制。方法采用双侧颈总动脉永久性结扎法构建VAD大鼠模型，将48只造模成功的大鼠随机分为模型组（生理盐水）、盐酸多奈哌齐组（阳性对照组，0.2g/kg）及YFXF低、高剂量组（12.18、24.36g/kg，以生药总量计），另设假手术组（生理盐水），每组12只。每天灌胃给药/生理盐水1次，连续30d。末次给药后，评估大鼠空间认知能力，观察其海马组织病理形态学变化，检测其血清中肿瘤坏死因子α（TNF-α）、白细胞介素4（IL-4）含量，检测其海马组织中GRB2/ERK/CRLS1通路相关蛋白及GRB2、CRLS1、NADH脱氢酶亚基1（ND1）、Tafazzin（TAZ）、磷脂移位酶3（PLSCR3）mRNA表达水平，并检测其海马组织中腺苷三磷酸（ATP）含量。结果与假手术组比较，模型组大鼠逃避潜伏期显著延长（P＜0.05），穿越平台次数显著减少（P＜0.05），并可见海马锥体细胞和尼氏小体数量锐减；血清中TNF-α含量显著升高（P＜0.05），IL-4含量显著降低（P＜0.05）；海马组织中GRB2蛋白表达水平、CRLS1蛋白表达水平、ERK蛋白的磷酸化水平以及GRB2、CRLS1、ND1、TAZ、PLSCR3mRNA相对表达量和ATP含量均显著降低（P＜0.05）。与模型组比较，各给药组大鼠海马组织中上述病理改变均有所缓解，各定量指标均显著回调（P＜0.05）。结论YFXF可能通过激活GRB2/ERK/CRLS1通路，维护心磷脂稳态，改善线粒体能量代谢，从而改善VAD模型大鼠海马神经元损伤。 |
| ABSTRACT： | OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism. |
| 期刊： | 2026年第37卷第07期 |
| 作者： | 卓桂锋；陈炜；朱小敏；符钰岚；张金枝；吴林 |
| AUTHORS： | ZHUO Guifeng，CHEN Wei，ZHU Xiaomin，FU Yulan，ZHANG Jinzhi，WU Lin |
| 关键字： | 益肺宣肺降浊方；血管性痴呆；神经元损伤；GRB2/ERK/CRLS1通路；线粒体；心磷脂 |
| KEYWORDS： | Yifei xuanfei jiangzhuo formula； vascular dementia； neuron injury； GRB2/ERK/CRLS1 pathway； mitochondria； |
| 阅读数： | 4 次 |
| 本月下载数： | 0 次 |
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